Blood coagulation detection device

ABSTRACT

This apparatus for detecting the time of coagulation of liquid blood samples includes a hypodermic syringe having the necessary components mounted therein to perform this test. These components include a group of spatially separated electrodes which are disposed around the exterior surface of either the plunger or the base of the barrel where the cannula normally mounts to the hypodermic syringe. Means are provided for connecting the electrodes to an impedance monitoring circuit to ascertain the clotting time of the sample.

United States Patent [151 3,674,012 Sage 1 July 4, 1972 my BLOOD COAGULATION DETECTION OTHER PUBLICATIONS DEVICE [72] Inventor: Stanley J. Sage, Lexington, Mass.

|73| Assignee: American Optical Corporation,

Southbridge, Mass.

|22| Filed: April [7, I970 (21 Appl. No: 29,563

[52] U.S.Cl. ..I28/2.I R [5]] ..A6Ib 5/04 [58] FieldolSeareh l28/2,2.l E,2.l Z,2.l R

{56] References Cited UNITED STATES PATENTS 3,000,805 9/1961 Carritt et al ..I28/2 3,078,850 2/1963 Schein et al. .....l28/2.l 2,555,937 6/l95l Rosenthal et al. .,...l28l2.l 2,637,316 5ll953 Grez r ..I28/2.l 3,224,433 12/1965 Dalebor.....................................128/2 FOREIGN PATENTS OR APPLICATIONS 950,4 l 5 2/l964 Great Britain ..l28/2 Method of Polarographic in vivo Continuous Recording of Blood Oxygen Tension; Science, Vol. 128 (Oct. I958).

Primary Examiner-Antonio F. Guida Assistant Examiner-H. Heinz Att0rney-William C. Nealon, Noble S. Williams, Robert 1. Bird and Bernard L. Sweeney [57] ABSTRACT This apparatus for detecting the time of coagulation of liquid blood samples includes a hypodermic syringe having the necessary components mounted therein to perform this test. These components include a group of spatially separated electrodes which are disposed around the exterior surface of either the plunger or the base of the barrel where the cannula normally mounts to the hypodermic syringe. Means are provided for connecting the electrodes to an impedance monitoring circuit to ascertain the clotting time of the sample.

I6 Claims, 9 Drawing Figures PATENTEUJUL 4W2 3,674,012 SHEET 10F 2 FIGS.

FIG.4.

INVENTOR STANLEY J. SAGE PATENTEDJUL 4mm 3.674012 SHEET 20F 2 I08 :i WV i: FIG .9.

I0 =6 b d:

HO I06 INVENTOR 2 STANLEY J. SAGE 0 \J AGE BLOOD COAGULATION DETECTION DEVICE BACKGROUND OF THE INVENTION This invention is related to blood testing apparatus and is more particularly concerned with improved apparatus for performing coagulation time tests on liquid blood samples.

A recently developed method of providing information concerning the coagulation time of a sample of blood drawn from a patient involves comparing the electrical impedance of the blood sample, before and during coagulation, against a blood sample which has had its coagulation retarded, usually by chemicals, for example, heparin.

The comparative impedance may be readily determined by a bridge circuit, with one side of the bridge monitoring the blood sample being tested, and the other side monitoring the control blood sample. It has been found that when the coagulation of the test sample commences, the impedance of the sample falls rapidly to substantially zero or some other minimum value. As clotting time progresses following the initial coagulation, the impedance of the test sample rises. The clotting time may be measured by using a continuously operating recorder on a time-scale which provides a visual record of the change of impedance per unit of time.

The present techniques used to perform this test introduce a chronological and environmental history such that only a very specially trained technician can acquire reproducable results and then only when he performs the test fairly frequently. Therefore, with the present apparatus. the newly developed technique loses much of its inherent value because the normal medical testing laboratories cannot perform the test. These erratic results arise from several sources, for example, contact with air, with biolo-gical fluids on the skin of the patient and/or technician, with residue in the apparatus from previous tests, from agitation of the sample between withdrawal from the patient and insertion into the apparatus, or time delay occuring between the insertion of fractions of the sample withdrawn from the patient into the test and control cells.

The present apparatus requires the removal of the blood sample from a patient either by syringe or by capillary tube and subsequent insertion into the narrow diameter tubing in the apparatus where the test cells are located. Generally the test and control cells are remote from each other such that a period of time elapses between the insertion of the two fractions into the apparatus. The test cells are located in this narrow diameter tubing because the cross-sectional dimensions of the test cell influence the clotting time. The greater the dimensions of the cell are, the longer the clotting time.

Some of these disadvantages may be overcome by using a narrow diameter pipette with the control coatings and electrodes located along its inner surface. However, similar to the previous apparatus, the disposition of these coatings and electrodes in the narrow diameter of the tubing is extremely difficult, expensive, and unreliable.

SUMMARY OF THE INVENTION Accordingly, it is an object of the present invention to provide apparatus for testing the coagulation time of a sample of blood by comparing the electrical impedance of test and control fractions of this sample in which reliable results may be gained by a medical technician, the only requirement of whom is that he be able to draw a blood sample properly.

Another object of the invention is to provide such apparatus which is associated with the hypodermic syringe which is used to withdraw the blood sample from the patient.

Another object of the invention is to provide such apparatus in which the electrodes are disposed on the exterior surface of the plunger or barrel of the hypodermic syringe.

A further object of the invention is to provide such ap paratus in which the test cells are disposed between the barrel and the plunger.

A still further object of the invention is to provide such apparatus in which either the hypodermic syringe or that portion thereof in which the test cells are located is disposable.

Briefly, the invention in its broadest aspect comprises an apparatus for use with an impedance monitoring circuit for determining the clotting time of a blood sample in which the apparatus includes a hypodermic syringe for withdrawing and retaining the blood sample from a patient. The hypodermic syringe is comprised of a barrel, a plunger, and a cannula. A plurality of spatially separated electrodes are attached to the syringe and engage the blood sample. The electrodes define a test cell and at least one control cell. The test cell is defined between a first pair of the plurality of electrodes and the control cell is defined between a second pair of the electrodes. Means are provided also for connecting the electrodes to the impedance monitoring circuit.

Further objects, advantages and features of the invention will be apparent in the arrangement and construction of the constituent parts in detail as set forth in the following specification taken together with the accompanying drawing.

DESCRIPTION OF THE DRAWING In the drawing,

FIG. 1 is a side elevational view of one form of a hypodermic syringe including means for connecting the electrodes in the hypodermic syringe to an impedance monitoring circuit;

FIG. 2 is an enlarged, partially broken-away, side elevational view, partially in cross-section showing the electrodes disposed about the lower end of the plunger;

FIG. 3 is a partial side elevational view of another form of the invention embodied on the end of the plunger;

FIG. 4 is an isometric view of the lower end of the plunger showing a third form of the invention;

FIG. 5 is an exploded side elevational view of a glass hypodermic syringe in which an adapter is provided between the barrel and cannula and in which the coagulation time tests may be performed;

FIG. 6 is an enlarged partial side elevational view of the base of the barrel shown in FIG. 5;

FIG. 7 is an enlarged cross-sectional view of another form of the adapter shown in FIG. 5 in which the electrodes are implaced in the adapter;

FIG. 8 is an electrical schematic of an impedance monitoring circuit which compares the impedance of a control sample against a test sample; and

FIG. 9 is an electrical schematic of another impedance monitoring circuit in which three control samples are utilized in conjunction with the test sample.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS In discussing the succeeding figures of the drawing, like reference numerals will refer to identical parts of the apparatus.

Referring initially to FIG. I, wherein there is shown a hypodermic syringe 10 which includes a barrel I2, a plunger 14 which has a thumbrest l6, and a cannula 18. The plunger 14 telescopes into the barrel l2 and the cannula 18 is fastened to the lower end or base of the barrel. Also shown is an exten sion 20 of the thumbrest 16 in which a connector, not shown, is located and is electrically attached to the electrodes at the base of the plunger as will be described more fully with reference to later figures. A jack 22 is shown for connecting the electrodes in the syringe to the impedance monitoring circuit. This type of connection allows the use of a disposable syringe or a portion of the syringe such as the plunger to be disposable and yet quickly connectable to the impedance monitoring circuit.

FIG. 2 is an enlarged, partially cross-sectional side elevational view of the lower end of the plunger 14 in position in the barrel 12. A plurality of electrodes 24 are disposed near the lower end of the plunger M. The electrodes are shown as four bands of conductive material 24a, 24b, 24c, and 24d around the lower end of the plunger I4. The electrodes are connected to the connector in the extension 20 at the top of the plunger by a like plurality of conductors 26. Included in this embodiment is a common conductive bus 28 which is disposed around the interior surface of the barrel 12. The lower end of the plunger 14 has two sections having constricted cross-sections 34 and 36. Section 34 has a larger diameter than section 36, and is, therefore, more closely located to the bus 28. Electrode 24a is located on the upper section 34 and a test cell 30 is defined between the section 34 of the plunger and the bus 28. The other three electrodes 24b, 24c, and 24d are located on the lower section 36 and define three control cell locations 32b, 32c, and 32d between section 36 and the bus 28.

The test cell 30 has a radial dimension between the section 34 and the bus 28 which, in the preferred embodiment, is approximately l-2 mm. This dimension is not critical, however, as mentioned previously, the coagulation time of the blood sample contained in the syringe is directly influenced by the cross-sectional dimensions of the container in which the sample is stored. Therefore, to reduce the test time to a workable period of approximately l-l minutes, a 1-2 mm space between the conductor 24a and the bus 28 is maintained. Similarly, a much greater radial dimension is present between the other conductors 24b, 24c, and 24d and the common bus 28. This greater area of the cells severely retards the coagulation of the blood contained in the control cells 32b, 32c, and 324'. Hence, the control cells provide a means for eliminating those factors which affect the impedance of the sample, but which are unrelated to the coagulation time of the blood sample, such as red blood cell sedementation or cooling of the sample. Thus the output from the impedance monitoring circuit reflects only the difference in impedance between the control and test samples due to the coagulation of the blood in the test sample.

It can be seen from the embodiment shown in FIG. 2, that the electrodes may be disposed about the plunger 14 of the syringe after the cell area sections have been formed thereon by any normal manufacturing technique. The conductors 26 are easily cast in the plunger I4. This is a far less expensive and more reliable method of manufacture than if the same closely controlled bands of material were to be placed along the inner diameter of a length of tubing, particularly when the tubing has an inner diameter of approximately I mm in order to reduce the coagulation time to a workable time period.

Referring now to FIG. 3, there is shown another means of placing the test and control cells on the outer surface of the plunger I4 on the lower end thereof. In this embodiment, there are only two cells formed, one control and one test cell. Only a single reduced area section 38 is formed at the end of the plunger 14 and four conductive band electrodes 24a, 24b, 24c, and 24d are located around the periphery of the section 38. The test cell is formed between the section 38 of the plunger and the barrel I2 and between the upper two electrodes 24a and 24b. A means 40 for retarding the coagulation rate, such as a silicone compound or an anti-coagulation enzyme is disposed around the periphery of section 38 and covering the area of the control cell which is formed between the section 38 and the barrel 12 and between electrodes 24c and 24d. In this case, as it can be seen, the common conductive bus is not necessary along the inner surface of the barrel l2 because the impedance measurements will be taken between the adjacent electrodes, rather than between the electrodes and the common bus.

FIG. 4 shows a further modification of the previously described apparatus. Herein, the electrodes are point contacts 42 which are located in a groove 44 in the side of the plunger 14. In this embodiment, a total of six electrodes 42a, 42b, 42c, 42c, 42c, and 42f are utilized. Two of the electrodes 42a and 42b are located in the upper tangential surface 46 in the groove 44 which is spaced approximately l-2 mm from the interior wall of the barrel 12. The remaining four electrodes 42c, 42d, 42e, and 42f are located on a second tangential surface 48 which is spaced at a greater distance from the interior surface of the barrel I2 thereby again creating a volume in which control cells may be located and in which the increased crosssectional area serves to retard the coagulation rate. An anticoagulant coating could be substituted for the increased area as above. Again the impedance measurements are made between adjacent electrodes rather than the electrodes and a common bus. Namely, the test cell electrodes 42a and 42b sense an impedance therebetween which is compared with the three control cells which are located between the electrodes 42c 42d, 42d 42c, and 42e 42f, respectively.

It should be appreciated, at this time, that any of the above combinations of electrode positions and cell definitions may be combined to define an apparatus which will successfully perform the prescribed test. One pair of the spatially separated electrodes may form the test cell while a second pair of the electrodes defines the control cell. Obviously, as in the case of the embodiment shown in FIG. 2, one electrode may be common to both the test and control cells. The preceding embodiments are directed to the formation of the apparatus for testing blood samples in a disposable syringe. This disposable character of the apparatus utilized in the test has the ad vantage that there is never any uncertainty concerning the presence of any residue in the apparatus from any previous tests.

Referring now to FIG. 5, an exploded view of a syringe and a disposable adapter therefore is shown. In this embodiment the syringe 50 utilized is the permanent glass type and a disposable adapter 52 is inserted between the cannula 54 and the barrel 56 of the syringe 50. The barrel 56 has a hollow tip 58 thereon onto which the cannula 54 normally attaches. However, in this embodiment, the adapter 52 is located therebetween and forms the chamber in which the test and control cells are located. The adapter 52 is now disposable such that the danger is again eliminated of retaining a residue of material from a previous test.

FIGS. 6 and 7 show two possible forms of the adapter 52 which may be derived from the general configuration of the adapter 52 to provide an apparatus for perfonning the prescribed test.

In FIG. 6, the electrodes 62a, 62b, 62c, and 62d are located around the periphery of the tip 58. The initial two electrodes 62a and 62b are located on a first radially diminished section 64, which is spaced from the end of the tip 58 by the width of the second radially diminished section 66. A test cell is formed between the adapter and section 64 when the adapter 52 is in place. Electrodes 62c and 62d form a control cell when the adapter 52 is in place; due to the increased radial dimension between the section 66 on which they are disposed and the inner diameter of the adapter 52, which is not shown in this figure for clarity, the coagulation rate is retarded.

A second form of the adapter is shown in the cross-sectional view in FIG. 7. In this form, point contact electrodes 70a, 70b, 70c, and 70d are embedded in the inner surface of the adapter 52 and form a test cell between electrodes 70a and 70b and a control cell between electrodes 70c and 70d.

Referring now to FIG. 8, there is shown an electrical schematic of a comparative bridge circuit which may be used with the embodiments of the apparatus which were described above which include only two cells; one for retaining a test fraction of the blood sample and one for the control fraction of the blood sample. These cells, the test and control cells, are connected to input terminals 800 and respectively. The circuit thereby places the test sample in the first arm of the bridge; the first arm being connected across terminals b and c of a double beam oscilloscope 92. The second arm of the bridge includes the control sample and is arranged in series with the first arm of the bridge and connected between terminals c and d of the oscilloscope 92. The third arm includes a compound resistor identified as R, which includes a 20 kilohm resistor 86 and a potentiometer 88 of l0 kilohm capacity. A variable trimmer capacitor 90 is connected in parallel across resistor R and, which in combination, are connected across terminals 0 and b of the oscilloscope 92. The capacitor 90 is an air-filled trimmer capacitor which is variable from 3 to 30 pico-farads. The fourth arm of the bridge is composed of a resistor 98, which is a 25 kilohm resistor, and a second variable trimmer capacitor 94 which is connected in parallel with the resistor 98. The fourth arm of the bridge is connected between terminals 0 and d of the oscilloscope 92. The double beam oscilloscope 92 has one beam which displays the voltage difference between the measuring terminals d and b and which typically uses a sweep rate of 20 micro-seconds per centimeter and a sensitivity of l millivolt per centimeter.

The other beam of the oscilloscope 92 monitors the electrical supply from an oscillator 96 which is applied at terminals a and c of the oscilloscope 92.

In operation, the apparatus of the invention has a sample of blood drawn from a patient into the syringe. The same sample nearly simultaneously fills both the test and control cells in the syringe and at which time, the timing of the test immediately commences. No uncertainty has been introduced due to a variable delay between withdrawal of the sample and the actual commencement. The bridge is then supplied with a hertz, l.2 volt signal which is obtained from the oscillator 96. The impedance of the test sample contained in the first arm of the bridge is then compared to the impedance of the control sample which is in the second arm of the bridge. The comparative impedance may be plotted on a graph, with time plotted along the abcissa and the resistance of the potentiometer 88, which is indicative of the relative impedance of the sample, plotted along die ordinate. A typical graph shows the impedance of the blood sample being very high initially, and with the lapse of time the resistance falls sharply to a minimum point coincident with the coagulation of the sample and then gradually rises over a longer period of time as coagulation continues.

FIG. 9 shows a modified arrangement of an impedance monitoring bridge circuit in which the circuit utilizes blood sample fractions in each of its four arms. Forms of the apparatus which provide four cells are detailed above. These sample cells are schematically shown and distinguished by reference numerals as 100, 102, 104, and 106. The pairs of diagonally opposite bridge terminals are shown at a,b and c,d. The resistance arm b,d contains a variable resistor 110 which balances the impedance monitoring bridge and the bridge arm a,d contains a small fixed resistor 108. With such an arrangement, the provision of trimmer capacitors is eliminated, as the capacitance of the individual cells, being identically constructed, is the same. In this circuit, the blood sample fractions in the control cells 100, I04, and 106 include means for retarding coagulation.

Hence, in one typical test chart, a resistance initially of 520 kilohms falls to about 275 kilohms in approximately a 10 minute interval; thereafier the resistance gradually increases over the next 30 minutes to approximately 450 kilohms. The coagulation time, therefore, is determined to be approximately l0 minutes. During this time, the bridge circuit is balanced by means of the potentiometer 88 or 110 at approximately one-half minute intervals throughout the test period. However, as the impedance rises, the time interval between readings may be increased. The impedance is determined at each balancing and this is the value which is plotted versus time to provide the test results. Mechanized recording by means of a continuously balancing bridge circuit may be used where a large scale test is desired. Other circuitry may, of course, be used to measure the relative impedance between the test and control samples.

While there have been shown and described what are considered to be preferred embodiments of the present invention, it will be obvious to those skilled in the art that various changes and modifications may be made therein without departing from the invention.

I claim:

1. Apparatus for use with an impedance monitoring circuit for determining the clotting time of a blood sample, the apparatus comprising a hypodermic syringe having a barrel, a plunger, and a cannula for withdrawing and retaining the blood sample from a patient,

a plurality of spatially separated electrodes attached to the syringe and engaging the blood sample, the electrodes defining a test cell and at least one control cell,

said test cell being defined between a first pair of said plurality of electrodes,

said control cell being defined between a second pair of said plurality of electrodes,

means associated with the control cells to retard the clotting of the blood sample fraction contained therein, and

means for connecting the electrodes to the impedance monitoring circuit.

2. Apparatus according to claim 1 in which the means for retarding comprises a coating of an anti-coagulating substance disposed on the surface of the control cells.

3. Apparatus according to claim 2 wherein the anti-coagulating substance is a silicone material.

4. Apparatus according to claim 2 wherein the anti-coagulating substance is a clot retarding enzyme impregnated into the surface of the control cells.

5. Apparatus according to claim 1 wherein the means for retarding comprises each of the control cells having a cross-sectional area which is greater than the cross-sectional area of the test cell.

6. Apparatus according to claim 1 wherein the plurality of spatially separated electrodes are disposed on the plunger adjacent the lower end thereof, and spaced from the interior wall of the barrel so as to define the test and control cells therebetween.

7. Apparatus according to claim 6 in which the spatially separated electrodes are a plurality of rings of conductive material disposed around the perimeter of the plunger.

8. Apparatus according to claim 6 in which the electrodes are point contacts.

9. Apparatus according to claim 6 which further includes a common conductive bus disposed on the inner wall of the barrel.

10. Apparatus according to claim 1 hypodermic syringe is disposable.

l 1. Apparatus according to claim I in which a hollow adapter is mounted between the barrel and the cannula and provides communication therebetween, the test and control cells being disposed between the barrel and the adapter.

12. Apparatus according to claim 11 in which the syringe is of the permanent type and the adapter is disposable.

13. Apparatus according to claim 1 1 wherein the electrodes are conductive bands disposed about the perimeter of the tip of the barrel adjacent to the base thereof.

14. Apparatus according to claim 10 wherein the electrodes are disposed in the adapter.

15. Apparatus according to claim 1 wherein one control cell is defined.

16. Apparatus according to claim 1 wherein three control cells are defined.

in which the i i t I 

1. Apparatus for use with an impedance monitoring circuit for determining the clotting time of a blood sample, the apparatus comprising a hypodermic syringe having a barrel, a plunger, and a cannula for withdrawing and retaining the blood sample from a patient, a plurality of spatially separated electrodes attached to the syringe and engaging the blood sample, the electrodes defining a test cell and at least one control cell, said test cell being defined between a first pair of said plurality of electrodes, said control cell being defined between a second pair of said plurality of electrodes, means associated with the control cells to retard the clotting of the blood sample fraction contained therein, and means for connecting the electrodes to the impedance monitoring circuit.
 2. Apparatus according to claim 1 in which the means for retarding comprises a coating of an anti-coagulating substance disposed on the surface of the control cells.
 3. Apparatus according to claim 2 wherein the anti-coagulating substance is a silicone material.
 4. Apparatus according to claim 2 wherein the anti-coagulating substance is a clot retarding enzyme impregnated into the surface of the control cells.
 5. Apparatus according to claim 1 wherein the means for retarding comprises each of the control cells having a cross-sectional area which is greater than the cross-sectional area of the test cell.
 6. Apparatus according to claim 1 wherein the plurality of spatially separated electrodes are disposed on the plunger adjacent the lower end thereof, and spaced from the interior wall of the barrel so as to define the test anD control cells therebetween.
 7. Apparatus according to claim 6 in which the spatially separated electrodes are a plurality of rings of conductive material disposed around the perimeter of the plunger.
 8. Apparatus according to claim 6 in which the electrodes are point contacts.
 9. Apparatus according to claim 6 which further includes a common conductive bus disposed on the inner wall of the barrel.
 10. Apparatus according to claim 1 in which the hypodermic syringe is disposable.
 11. Apparatus according to claim 1 in which a hollow adapter is mounted between the barrel and the cannula and provides communication therebetween, the test and control cells being disposed between the barrel and the adapter.
 12. Apparatus according to claim 11 in which the syringe is of the permanent type and the adapter is disposable.
 13. Apparatus according to claim 11 wherein the electrodes are conductive bands disposed about the perimeter of the tip of the barrel adjacent to the base thereof.
 14. Apparatus according to claim 10 wherein the electrodes are disposed in the adapter.
 15. Apparatus according to claim 1 wherein one control cell is defined.
 16. Apparatus according to claim 1 wherein three control cells are defined. 